1,721,197 research outputs found
Modulation of Acute and Chronic Inflammation of the Lung by GITR and its Ligand
No full textGlucocorticoid-induced TNFR-related (GITR) protein, a member of the tumor necrosis factor receptor superfamily, is expressed in many components of the innate and adaptive immune system and modulates their activation following interaction with its ligand (GITRL). Here we review and discuss results described in previous publications where the role of the GITR/GITRL system in lung inflammation was evaluated using two experimental systems. We also discuss the proinflammatory role played by the GITR/GITRL system and the potential use of GITR fusion protein in inhibiting inflammation
Effect of stress on the paracellular barrier in the rat ileum
No full textBackground: Restraint stress induces permeability changes in the rat small intestine but little is known of the ultrastructural events leading to defects of the paracellular sealing or of the short term evolution of these alterations.
Methods: In the present study, we performed transmission electron microscopy in the terminal ileum perfused with lanthanum after two hours of immobilisation stress and in non-stressed control rats. Moreover, immunohistochemistry of the tight junction (TJ) associated proteins, occludin and zonula occludens 1 (ZO-1), was carried out together with western blot analysis of the transmembrane protein occludin. TJ morphology was also assessed after a 22 hour recovery period.
Results: Immobilisation stress induced a significant increase in epithelial permeability to the lanthanum tracer (p<0.005) which recovered completely after 22 hours. Compared with unstressed controls, in stressed rats no differences were found on freeze fracture analysis. The TJ related immunofluorescence signals of occludin and of ZO-1 were irregularly distributed in stressed rats after two hours but returned to a normal pattern at 24 hours although with minor intensity. No quantitative alterations in occludin were detectable in stressed rats by immunoblot whereas a perinuclear concentration of occludin was observed by immunolocalisation.
Conclusions: Immobilisation stress induced an increase in TJ permeability in the rat terminal ileum. These changes were mainly due to modifications and redistribution of the TJ transmembrane protein occludin and of the plaque protein ZO-1 whereas protein synthesis, at least that of occludin, was not affected by stress
Will Cannabigerol Trigger Neuroregeneration after a Spinal Cord Injury? An In Vitro Answer from NSC-34 Scratch-Injured Cells Transcriptome
No full textSpinal cord injury affects the lives of millions of people around the world, often causing disability and, in unfortunate circumstances, death. Rehabilitation can partly improve outcomes and only a small percentage of patients, typically the least injured, can hope to return to normal living conditions. Cannabis sativa is gaining more and more interest in recent years, even though its beneficial properties have been known for thousands of years. Cannabigerol (CBG), extracted from C. sativa, is defined as the “mother of all cannabinoids” and its properties range from anti-inflammatory to antioxidant and neuroprotection. Using NSC-34 cells to model spinal cord injury in vitro, our work evaluated the properties of CBG treatments in motor neuron regeneration. While pre-treatment can modulate oxidative stress and increase antioxidant enzyme genes, such as Tnx1, decreasing Nos1 post-treatment seems to induce regeneration genes by triggering different pathways, such as Gap43 via p53 acetylation by Ep300 and Ddit3 and Xbp1 via Bdnf signaling, along with cytoskeletal remodeling signaling genes Nrp1 and Map1b. Our results indicate CBG as a phytocompound worth further investigation in the field of neuronal regeneration
5-lipoxygenase modulates the alteration of paracellular barrier function in mice ileum during experimental colitis
No full textSmall intestine permeability is frequently altered in inflammatory bowel disease and may be caused by the translocation of intestinal toxins through leaky small intestine tight junctions (TJs) and adherence. Recently, it has been shown that 5-lipoxygenase (5-LO) plays an important role in the development of various inflammatory conditions like inflammatory bowel disease. In the present study, by comparing the responses in wild-type mice (5-LOWT) with those of mice lacking the 5-lipoxygenase (5-LOKO), we investigated the role played by this enzyme in the permeability and structure of small intestine TJs in an animal model of experimental colitis. To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). Four days after colitis induction by DNBS, the ileal TJs were studied by means of transmission electron microscopy using lanthanum nitrate and immunohistochemistry of occludin and ZO-1. When compared with DNBS-treated 5-LOWT mice, DNBS-treated 5-LOKO mice experienced a reduced rate of the extent and severity of the histological signs of colon injury. After administration of DNBS, 5-LOWT mice showed a significant increase of ileal permeability (88.3% ± 1.2%) compared with sham (5.6% ± 0.5%). In colitis, the percentage of "leaky" junctions in terminal ilea correlated positively with the macroscopic colon damage score. Distal colitis in 5-LOWT mice induces an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. On the contrary, a significant reduction of (1) the degree of colon injury, (2) the alteration of ZO-1 and occludin localization (immunohistochemistry), and (3) ileal permeability (8.1% ± 0.7%) caused by DNBS in the colon was observed in 5-LOKO mice. Similarly, the treatment of 5-LOWT with zileuton (50 mg/ kg per oral gavage twice a day), a 5-LO inhibitor, resulted in a significant reduction of all the previously described parameters. Taken together, our results clearly demonstrate that 5-LO modulates small intestinal permeability in experimental colitis through the regulation of TJ protein. Copyright © 2006 by the Shock Society
Cannabidiol exerts protective effects in an in vitro model of Parkinson's disease activating AKT/mTOR pathway
No full textParkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of the nigrostriatal dopaminergic pathway with loss of substantia nigra pars compacta neurons and dopamine depletion. Various natural compounds showed protective actions against PD. In this work, the protective effects of cannabidiol (CBD), obtained from Cannabis sativa, were evaluated in retinoic acid differentiated SH-SY5Y cells exposed to 1-methyl-4-phenylpyridinium (MPP+), an in vitro PD model. In order to evaluate which receptor is involved in CBD actions CB1, CB2 and TRPV1 receptor antagonists were used. CBD counteracted the loss of cell viability caused by MPP+, reducing apoptosis as demonstrated by the reduction of Bax and caspase 3. Moreover, CBD reduced the nuclear levels of PARP-1. The protective effects of CBD seem to be mediated by the activation of ERK and AKT/mTOR pathways. The treatment with AKT1/2 inhibitor and the mTOR inhibitor rapamycin abolished CBD protective effects. The CBD-induced ERK activation may be mediated by CBD interaction with CB2 and TRPV1. We also investigated the protein levels of the autophagic proteins LC3 and beclin 1. CBD reduced the MPP+-induced increase of LC3 by CB2 and TRPV1 receptors. These data suggested the involvement of ERK in the modulation of autophagy. However, beclin 1 levels were not modified neither by MPP+ nor by CBD. These results indicated that CBD may exert preventive and protective actions in PD
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Tyrphostin AG 126 reduces intestinal ischemia-reperfusion injury in the rat
No full textIn this study, we evaluated the effect of tyrphostin AG126, a tyrosine kinase inhibitor, in the splanchnic artery occlusion (SAO) shock mediated injury. SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min. After 1 h of reperfusion, SAO shocked rats developed a significant fall in mean arterial blood pressure. Ileum analysis revealed that SAO shock is characterized by a significant (P<0.01) induction in TNF-alpha and IL-1 ileum levels, while immunohistochemistry examination of necrotic ileum demonstrated a marked increase in the immunoreactivity in intracellular adhesion molecule (ICAM-1) and nitrotyrosine formation. A significant increase in myeloperoxidase activity (P<0.01) was also observed in rats subjected to ischemia-reperfusion injury. Tyrphostin AG126, given intraperitoneally 30 min before ischemia at the dose of 5 mg/kg, significantly improved mean arterial blood pressure, markedly reduced TNF-alpha and IL-1beta levels and the positive staining of ICAM-1 into the reperfused ileum. Tyrphostin AG126 significantly improved the histological status of the reperfused tissue. In conclusion, this study demonstrates that tyrphostin AG126 exerts multiple protective effects in splanchnic artery occlusion/reperfusion shock and suggests that this tyrosine kinase inhibitor may be a candidate for consideration as a therapeutic intervention for ischemia-reperfusion injury
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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